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CASE REPORT

Malignant Fibrous Histiocytoma Of Bone After Humerus Fracture

Antonio Jimenez-Martin *, Ricardo Mena-Bernal-Escobar#, Rafael Vazquez-Garcia #*

* Department of Orthopaedic Surgery, Valme University Hospital, Seville, Spain.
# Research Unit, Valme University Hospital, Seville, Spain.

Address for Correspondence

Antonio Jimenez-Martin.
Urb. Al-Alba, c/ Brisa 10-D.  41020. Seville.
Spain.
Tel: 34-609012308.
E-mail: antonio_jimenez10@hotmail.com

Abstract
 
A case of humerus fracture associated with malignant fibrous histocytoma in an 83 year old woman is presented. Malignant fibrous histiocytoma of the bone, is a condition that involves the humerus in 8% of cases and represents less than 1% of primary bone tumours. The patient with humeral shaft fracture treated with Hackethalís technique was presented three months later with tumefaction of the arm and osteolysis in the radiograph. Diagnosis of malignant fibrous histiocytoma of the bone after humerus fracture was confirmed by Cancer Antigen 15-3, CA 19-9, gammagraphy, MRI and biopsy. Early diagnosis with actin antibody HHF35, alpha smooth muscle actin, bone morphogenic protein-2 (BMP2), human p52-binding protein (MDM2), p53 gene and p21WAF-1 gene are emphasized. Treatment options, including surgery, radiotherapy (15-45 Gy) and chemotherapy (methotrexate, adriamycin, ifosfamide, cisplatin and doxorubicin, with new alternatives like ST1571, flavopiridol or Apo2L) are also reviewed.
Key words: histiocytoma, malignant, bone, ST1571, Apo2L, humerus, fracture.

J.Orthopaedics 2007;4(1)e4

Introduction:

Malignant fibrous histiocytoma of the bone (MFHB) is a rare primary disease representing less than 1% of bone tumours[1].  MFHB occurrs primarily in long bones (femur 44%, tibia 21% and humerus 8%).  We present a case report of MFHB in humeral fracture of the elderly, highlighting the importance of early diagnosis, in preventing later complications. Although imaging techniques or biopsy could confirm diagnosis, tumour markers are very useful for the early diagnosis of MFHB when it is suspected in fractures of the elderly.

Case Report:

A 83-year-old woman had an accidental fracture of the proximal third of the right humerus, that was reduced and stabilized by Hackethalís intramedullary bundle pinning.  A trephine biopsy of the osteolytic humeral wound taken at this time provided no pathological findings. The patient was readmitted three months later after the verification of a tumoration with stony consistency in the proximal third of the right arm without either fever or local signs of infection (Figure 1). No secretions or other data of interest were noted at the entry zones of the Kirschnerís wires and shoulder anteversion and abduction were very painful for the patient. 

Radiography showed that the Hackethalís technique was well tolerated, but with intense osteolysis at the focus of the fracture (Figure 2). Tumour markers were requested and normal results for Cancer Antigen (CA) 15-3 (17.8 IU/ml) and CA 19-9 (5.8 IU/ml) were obtained.  The level of alkaline phosphatase was 161 IU/L (upper normal limit of 104 IU/L) by biochemical analysis. IgA level was 598 mg/dl as compared to the upper normal limit of 390 mg/dL, but IgG and IgM were within the normal limits. The haemogram was normal and the ESR was 37 mm/h.  Magnetic resonance imaging (MRI)  showed an oval mass (10 x 9 cm), related to the proximal third of the humerus diaphysis and the deltoid muscle, with lobate contours of mixed signal and heterogeneous internal structure (Figure 3). Bone gammagraphy images suggested pseudoarthrosis in the proximal third of the right humerus (Figure 4).  In addition, a zone of osteolysis was found in the head of the humerus with a possible haematoma, tumour or abscess in the soft tissue.  There was an increase in osteoblastic activity in the remainder of the bony structures of the upper arm.  Senography of the patient showed mammary fat with calcifications of benign radiological aspect in both breasts but without radiological evidence of malignancy and RAPS negative.  A biopsy was taken and pathological examination showed bone material with malignant fusocellular tumour of storiform pattern which is highly suggestive of malignant fibro histiocytoma. 

The patient was diagnosed with malignant fibrous histiocytoma of the proximal third of the right humerus with pathological fracture (first episode), and was evaluated by the Oncology Service.  After the possibility of amputation was ruled out, local palliative radiotherapy in combination with chemotherapy was started, to relieve the tumefaction of the zone.  The patient received analgesia according to the guidelines of the Pain Unit of our institution.

Discussion :

Malignant fibrous histiocytoma of the bone (MFHB) manifests as a palpable mass in half the cases and/or as a painful tumoration in more than 75% of the cases. MFHB could occur  in a spontaneous fracture in 10% of the cases and is visible in the x-ray as a lytic formation, metaphysary, often with a moth-eaten appearance of the cortical reduction. MFHB could appear after radiation, neurofibromatosis or after osteosynthesis of fractures, as it appeared after the Hackethalís osteosynthesis in the present case report. Schuh et al.[2] reported a malignant fibrous histiocytoma after hip arthroplasty.

MFHB diagnosis may be suspected with gammagraphy, computerized axial tomography or magnetic resonance imaging (MRI) but it is confirmed only by histopathology of the biopsy. Different histopathologic forms such as fibroblastic with fascicular rupture, histiocytic with vimentin filaments, or similar to giant cell sarcomas may be observed. Usually, diagnosis of MFHB is made too late as in our case report. Therefore we suggest that molecular diagnosis is essential for an early diagnosis of MFHB. Ueda[3] used anti-muscle actin monoclonal antibody HHF35, alpha smooth muscle actin (alpha SMA) and bone morphogenetic protein (BMP-2) as markers for MFHB[4]. Mutations[5] in p53, alterations in MDM2 gene and expression of p21WAF-1 gene have been reported in histological studies[6].

Pathologies such as benign giant cell tumours, fibrosarcomas, fibroblastic osteosarcomas and metastasis of the carcinomas should be considered for the differential diagnosis of MFHB. 

MFHB progresses rapidly as seen in our case report and can advance quickly via the lymphatic route, with a survival rate at 15 years of 37% of the cases. Campanacci[7] reported remission survival rates of 40% and 21% for patients affected with primary or secondary MFHB, respectively.

Resective surgery (including pseudo capsule, better than marginal or contaminated surgery) and chemotherapy appear to be the most promising therapeutic alternatives since local control of the illness could be achieved in 70-80% of cases if the diagnosis and surgery are performed early[8].  Results depend on the extent of resection margins, as well as the presence of metastasis, neoplastic embolisms or metastatic lymphatic nodules.

Our patient received chemotherapy. Surgery with chemotherapy (methotrexate) is considered efficacious in 80% of cases with subsequent functional improvement. The best therapeutic protocol consists of high pre-operative doses of methotrexate, followed by extensive resection followed by post-operative chemotherapy with high doses of methotrexate plus adriamycin, ifosfamide and/or cisplatin. Using this protocol, remissions are achieved in 60% of the cases, although others have used doxorubicin and cisplatin as alternative chemotherapies   Recently, imatinib mesylate STI571 has been considered as a possible chemotherapeutic agent since it depresses tyrosine-kinase activity in a study of four malignant fibrous histiocytoma cell lines (TNMY1, GBS-1, Nara-F and Nara-H) with encouraging results.  Flavopiridol, a powerful inhibitor of the cell cycle at G1 and G2 phases in vitro, has proven to be effective in 61-64% of the malignant fibrous histiocytoma cell lines[9].  Treatment with cytokines (tumour necrosis factor-related apoptosis-inducing ligand - TRAIL/Apo2L -) combined with doxorubicin was described as another new therapeutic alternative by increasing rate of apoptosis[10]. 

Finally, our patient received radiotherapy too, as indicated in cases without complete surgical eradication of the disease. Radiotherapy (15-45 Gy) may also be used in combination with surgery for better local control of the illness in patients without metastases.

Reference :

  1. Joo M, Lee GJ, Koh YC, Kwon OK, Park YK. Primary intraosseous malignant fibrous histiocytoma of the skull: a case report. J Korean Med Sci.2003 Aug;18(4):609-13. 

  2. Schuh A, Zeiler G, Holzwarth U, Aigner T. Malignant fibrous histiocytoma at the site of a total hip arthroplasty. Clin Orthop.2004 Aug(425):218-22.

  3.   Ueda T, Araki N, Mano M, Myoui A, Joyama S, Ishiguro S, et al. Frequent expression of smooth muscle markers in malignant fibrous histiocytoma of bone. J Clin Pathol.2002 Nov;55(11):853-8. 

  4. Asano N, Yamakazi T, Seto M, Matsumine A, Yoshikawa H, Uchida A. The expression and prognostic significance of bone morphogenetic protein-2 in patients with malignant fibrous histiocytoma. J Bone Joint Surg Br.2004 May;86(4):607-12. 

  5. Gazziola C, Cordani N, Wasserman B, Carta S, Colombatti A, Perris R. Malignant fibrous histiocytoma: a proposed cellular origin and identification of its characterizing gene transcripts. Int J Oncol.2003 Aug;23(2):343-51. 

  6. Kawaguchi K, Oda Y, Sakamoto A, Saito T, Tamiya S, Iwamoto Y, et al. Molecular analysis of p53, MDM2, and H-ras genes in osteosarcoma and malignant fibrous histiocytoma of bone in patients older than 40 years. Mod Pathol.2002 Aug;15(8):878-88. 

  7. Campanacci M, Olmi R. Fibrosarcoma of bone. A study of 114 cases. Ital J Orthop Traumatol 1977;3:199-206. 

  8. Buchner M, Bernd L, Zahlten-Hinguranage A, Sabo D. Primary malignant tumours of bone and soft tissue in the elderly. Eur J Surg Oncol.2004 Oct;30(8):877-83. 

  9. Honoki K, Yoshitani K, Tsujiuchi T, Mori T, Tsutsumi M, Morishita T, et al. Growth inhibition and induction of apoptosis by flavopiridol in rat lung adenocarcinoma, osteosarcoma and malignant fibrous histiocytoma cell lines. Oncol Rep.2004 May;11(5):1025-30. 

  10. Clayer M, Bouralexis S, Evdokiou A, Hay S, Atkins GJ, Findlay DM. Enhanced apoptosis of soft tissue sarcoma cells with chemotherapy: A potential new approach using TRAIL. J Orthop Surg (Hong Kong).2001 Dec;9(2):19-22. 

This is a peer reviewed paper 

Please cite as : Antonio Jimenez-Martin:Malignant Fibrous Histiocytoma Of Bone After Humerus Fracture

J.Orthopaedics 2007;4(1)e4

URL: http://www.jortho.org/2007/4/1/e4

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